Piperidine → HCID 59226716, compound

HRID 1045046Notes

Reaction equation

HRID 1045046 reaction equation
[CH3:1][S:2][C:3]1[S:7][C:6]([CH:8]=O)=[CH:5][CH:4]=1.Cl.[C:11]([O:15][C:16](=[O:20])[CH2:17][CH2:18][NH2:19])([CH3:14])([CH3:13])[CH3:12].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C([N:52]=[C:53]=[S:54])(OCC1C2C(=CC=CC=2)C2C1=CC=CC=2)=O.N1CCCCC1>C(Cl)Cl>[C:11]([O:15][C:16](=[O:20])[CH2:17][CH2:18][N:19]([CH2:8][C:6]1[S:7][C:3]([S:2][CH3:1])=[CH:4][CH:5]=1)[C:53]([NH2:52])=[S:54])([CH3:14])([CH3:13])[CH3:12]

Participants

7

Reactant 5

HCID 8082PiperidineHCID 27369975-(Methylsulfanyl)thiophene-2-carbaldehydeHCID 4154759Fmoc isothiocyanateHCID 5049666Sodium triacetoxyborohydrideHCID 16218890Tert-butyl 3-aminopropanoate hydrochloride

Product 1

HCID 59226716HCID 59226716, compoundYield 66.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A mixture of 5-methylsulfanyl-thiophene-2-carbaldehyde (1.0 g, 6.3 mmol) and 3-amino-propionic acid tert-butyl ester hydrochloride (1.02 g, 7 mmol) in DCM (20 mL) was stirred at RT for 15 min. Sodium triacetoxyborohydride (2 g, 9.45 mmol) was added and the reaction was stirred at room temperature overnight. The reaction mass was partitioned between aqueous sodium bicarbonate and DCM. The organic layer was dried over sodium sulfate and concentrated to give the crude 3-[(5-methylsulfanyl-thiophen-2-ylmethyl)-amino]-propionic acid tert-butyl ester (800 mg, 38% yield). This crude amine (800 mg, 2.4 mmol) was dissolved in DCM (10 mL) and Fmoc-isothiocyanate (740 mg, 2.6 mmol) was added. After stirring the reaction overnight at room temperature, piperidine (3 mL) was added and the deprotection reaction was stirred for 30 min. The reaction mixture was concentrated and purified using a silica gel column. Concentration of the appropriate fractions under vacuum gave the desired thiourea (600 mg, 63% yield). This material is unstable and should be kept in the cold to prevent decomposition by cyclization and loss of t-BuOH. LC-MS m/z: 347 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 6.85 (d, 1H), 6.82 (d, 1H), 5.85 (s, 2H), 3.52 (t, 2H), 2.65 (t, 2H), 2.41 (s, 3H), 2.38 (s, 3H), 1.38 (s, 9H).

Workup

  1. stirringthe reaction was stirred at room temperature overnight
  2. customThe reaction mass was partitioned between aqueous sodium bicarbonate and DCM
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated
  5. customto give the crude 3-[(5-methylsulfanyl-thiophen-2-ylmethyl)-amino]-propionic acid tert-butyl ester (800 mg, 38% yield)
  6. stirringAfter stirring
  7. customthe reaction overnight at room temperature
  8. customthe deprotection reaction
  9. stirringwas stirred for 30 min
  10. concentrationThe reaction mixture was concentrated
  11. custompurified

Sources & evidence

ORD record
ord-547b98c2fafe453bab2de034fc3d37e4
Source dataset
uspto-grants-2013_10
Patent number
US08563742B2

Reaction notes

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